RESUMO
Breast cancer is a malignant tumor, which has derived from cells of the breast. Further, a relatively rapid metastasis, and resistance development against all the conventional drug combinations are major clinical issues in breast cancer patients as well as limitations like toxicity, genetic mutation, and metastasis make difficult the use of conventional therapy methods such as chemotherapy, radiotherapy, and local surgery. Therefore, considering the urgent needs, and high death rate in breast cancer cases, the development of new diagnosis and treatment regimens which diagnosed at the early stage and protected normal tissues required for clinical applications. Recently, the combination of tumor diagnosis and treatment within a single platform is a novel perspective, and magnetic nanoparticles are potential candidate owing to their low toxic effect, biocompatibility, biological degradability, superior magnetic properties, and targeting ability to overcome the problems of conventional diagnosis and therapy techniques. Considering these restrictions and requirements, the goal of this research was to investigate the potential of an innovative theranostic agent, which is soybean oil-based polystyrene (PS)-g-soybean oil graft copolymer containing AgNPs (PS-Agsbox) for treatment and MRI-based diagnosis of cancer. Herein, we designed targeted magnetic PS-Agsbox nanoparticles carrying thymoquinone (TQ) that is known for its anticancer potential against breast cancer, and herceptin (HER), which is to bind to the HER2 receptor protein on the surface of HER2-positive tumor cells, and acts by blocking the effects of it. We have successfully demonstrated selective binding, effective uptake of HER-conjugated magnetic PS-Agsbox nanoparticles into MDA-MB-231 (human breast carcinoma cells, a HER2-underexpressing cell line) and SKBR-3 (human breast cancer cells, a HER2-overexpressing breast cancer cell line) cell lines while no effect against L929 (mouse fibroblast cell line). Moreover, the magnetic resonance (MRI) properties of HER-conjugated magnetic PS-Agsbox nanoparticles were also confirmed.
Assuntos
Neoplasias da Mama , Nanopartículas , Animais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Poliestirenos/uso terapêutico , Medicina de Precisão , Óleo de Soja , Trastuzumab/uso terapêuticoRESUMO
The use of magnetic nanoparticles (MNPs) magnetized on applying an alternating magnetic field (AMF) to stimulate the thermal characteristics and to induce tumor apoptosis is a currently active area of research in cancer treatment. In previous work, we developed biocompatible and superparamagnetic polystyrene-sulfonic-acid-coated magnetic nanoparticles (PSS-MNPs) as applications for magnetically labeled cell trapping, but without assessment of treatment effects on tumor diseases. In the present work, we examined PSS-MNP-induced magnetic fluid hyperthermia (MFH) on SK-Hep1 hepatocellular carcinoma (HCC) cells for lethal thermal effects with a self-made AMF system; an adjustable AMF frequency generated a variable intensity of magnetic field and induced MNP relaxation. The extracellular and intracellular MFH treatments on a SK-Hep1 cell line were implemented in vitro; the result indicates that the lethal effects were efficient and caused a significantly decreased cell viability of SK-Hep1 cells. As the PSS-MNP concentration decreased, especially in intracellular MFH treatments, the MFH effects on cells, however, largely decreased through heat spreading to the culture medium. On controlling and decreasing the volume of culture medium, the problem of heat spreading was solved. It can be consequently expected that PSS-MNPs would be a prospective agent for intracellular cancer magnetotherapy.
Assuntos
Carcinoma Hepatocelular/terapia , Hipertermia Induzida/métodos , Neoplasias Hepáticas/terapia , Nanopartículas de Magnetita/uso terapêutico , Poliestirenos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular , HumanosRESUMO
BACKGROUND: Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as sodium polystyrene sulfonate and calcium polystyrene sulfonate, are widely used but may lead to constipation and other adverse gastrointestinal (GI) symptoms, reducing their tolerability. Patiromer and sodium zirconium cyclosilicate are newer ion exchange resins for treatment of hyperkalaemia which may cause fewer GI side-effects. Although more recent studies are focusing on clinically-relevant endpoints such as cardiac complications or death, the evidence on safety is still limited. Given the recent expansion in the available treatment options, it is appropriate to review the evidence of effectiveness and tolerability of all potassium exchange resins among people with CKD, with the aim to provide guidance to consumers, practitioners, and policy-makers. OBJECTIVES: To assess the benefits and harms of potassium binders for treating chronic hyperkalaemia among adults and children with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating potassium binders for chronic hyperkalaemia administered in adults and children with CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risks of bias and extracted data. Treatment estimates were summarised by random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD), with 95% confidence interval (CI). Evidence certainty was assessed using GRADE processes. MAIN RESULTS: Fifteen studies, randomising 1849 adult participants were eligible for inclusion. Twelve studies involved participants with CKD (stages 1 to 5) not requiring dialysis and three studies were among participants treated with haemodialysis. Potassium binders included calcium polystyrene sulfonate, sodium polystyrene sulfonate, patiromer, and sodium zirconium cyclosilicate. A range of routes, doses, and timing of drug administration were used. Study duration varied from 12 hours to 52 weeks (median 4 weeks). Three were cross-over studies. The mean study age ranged from 53.1 years to 73 years. No studies evaluated treatment in children. Some studies had methodological domains that were at high or unclear risks of bias, leading to low certainty in the results. Studies were not designed to measure treatment effects on cardiac arrhythmias or major GI symptoms. Ten studies (1367 randomised participants) compared a potassium binder to placebo. The certainty of the evidence was low for all outcomes. We categorised treatments in newer agents (patiromer or sodium zirconium cyclosilicate) and older agents (calcium polystyrene sulfonate and sodium polystyrene sulfonate). Patiromer or sodium zirconium cyclosilicate may make little or no difference to death (any cause) (4 studies, 688 participants: RR 0.69, 95% CI 0.11, 4.32; I2 = 0%; low certainty evidence) in CKD. The treatment effect of older potassium binders on death (any cause) was unknown. One cardiovascular death was reported with potassium binder in one study, showing that there was no difference between patiromer or sodium zirconium cyclosilicate and placebo for cardiovascular death in CKD and HD. There was no evidence of a difference between patiromer or sodium zirconium cyclosilicate and placebo for health-related quality of life (HRQoL) at the end of treatment (one study) in CKD or HD. Potassium binders had uncertain effects on nausea (3 studies, 229 participants: RR 2.10, 95% CI 0.65, 6.78; I2 = 0%; low certainty evidence), diarrhoea (5 studies, 720 participants: RR 0.84, 95% CI 0.47, 1.48; I2 = 0%; low certainty evidence), and vomiting (2 studies, 122 participants: RR 1.72, 95% CI 0.35 to 8.51; I2 = 0%; low certainty evidence) in CKD. Potassium binders may lower serum potassium levels (at the end of treatment) (3 studies, 277 participants: MD -0.62 mEq/L, 95% CI -0.97, -0.27; I2 = 92%; low certainty evidence) in CKD and HD. Potassium binders had uncertain effects on constipation (4 studies, 425 participants: RR 1.58, 95% CI 0.71, 3.52; I2 = 0%; low certainty evidence) in CKD. Potassium binders may decrease systolic blood pressure (BP) (2 studies, 369 participants: MD -3.73 mmHg, 95%CI -6.64 to -0.83; I2 = 79%; low certainty evidence) and diastolic BP (one study) at the end of the treatment. No study reported outcome data for cardiac arrhythmias or major GI events. Calcium polystyrene sulfonate may make little or no difference to serum potassium levels at end of treatment, compared to sodium polystyrene sulfonate (2 studies, 117 participants: MD 0.38 mEq/L, 95% CI -0.03 to 0.79; I2 = 42%, low certainty evidence). There was no evidence of a difference in systolic BP (one study), diastolic BP (one study), or constipation (one study) between calcium polystyrene sulfonate and sodium polystyrene sulfonate. There was no difference between high-dose and low-dose patiromer for death (sudden death) (one study), stroke (one study), myocardial infarction (one study), or constipation (one study). The comparative effects whether potassium binders were administered with or without food, laxatives, or sorbitol, were very uncertain with insufficient data to perform meta-analysis. AUTHORS' CONCLUSIONS: Evidence supporting clinical decision-making for different potassium binders to treat chronic hyperkalaemia in adults with CKD is of low certainty; no studies were identified in children. Available studies have not been designed to measure treatment effects on clinical outcomes such as cardiac arrhythmias or major GI symptoms. This review suggests the need for a large, adequately powered study of potassium binders versus placebo that assesses clinical outcomes of relevance to patients, clinicians and policy-makers. This data could be used to assess cost-effectiveness, given the lack of definitive studies and the clinical importance of potassium binders for chronic hyperkalaemia in people with CKD.
Assuntos
Quelantes/uso terapêutico , Terapia por Quelação/métodos , Hiperpotassemia/tratamento farmacológico , Potássio , Insuficiência Renal Crônica/complicações , Idoso , Causas de Morte , Quelantes/efeitos adversos , Terapia por Quelação/efeitos adversos , Doença Crônica , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/mortalidade , Pessoa de Meia-Idade , Polímeros/efeitos adversos , Polímeros/uso terapêutico , Poliestirenos/efeitos adversos , Poliestirenos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Silicatos/efeitos adversos , Silicatos/uso terapêuticoRESUMO
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γENaC subunit in the PHA-I phenotype. Nephron-specific γENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or ßΕΝaC, an HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase NCC activation. However, when K+ was eliminated from the diet at the time that γENaC was deleted, plasma K+ concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced ßENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K+ concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na+ balance in γENaC-deficient mice.
Assuntos
Canais Epiteliais de Sódio/genética , Hiperpotassemia/genética , Potássio/sangue , Pseudo-Hipoaldosteronismo/sangue , Pseudo-Hipoaldosteronismo/genética , Animais , Quelantes/uso terapêutico , Suplementos Nutricionais , Hiperpotassemia/sangue , Hiperpotassemia/tratamento farmacológico , Camundongos , Camundongos Knockout , Néfrons , Poliestirenos/uso terapêutico , Potássio na Dieta/administração & dosagem , Sódio na Dieta/administração & dosagem , Membro 3 da Família 12 de Carreador de Soluto/metabolismoRESUMO
PURPOSE: A case of episodic hyperkalemia associated with daptomycin administration is reported. SUMMARY: A 46-year-old African-American woman was hospitalized for treatment of a shoulder abscess. Initially treated with i.v. vancomycin, the patient was switched to daptomycin 9 mg/kg i.v. (500 mg daily) after three days. On day 10 of daptomycin therapy, she was noted to have a serum potassium concentration of 5.4 meq/L, with an increase to 6.1 meq/L on day 11. Reversal of hyperkalemia was achieved with oral sodium polystyrene sulfonate and other agents, and daptomycin was withheld for one day, during which time the patient's serum potassium level normalized. One day after daptomycin therapy was resumed at a lower dose (7 mg/kg), the potassium concentration increased again (to 5.5 meq/L). With a further dosage reduction and continued administration of sodium polystyrene sulfonate, the patient completed the full course of daptomycin therapy. There was a close temporal relationship between daptomycin administrations and the serum potassium fluctuations; other potential causes of hyperkalemia were ruled out. Evaluation of this case using the algorithm of Naranjo et al. yielded a score of 6, indicating that the serum potassium elevations probably constituted an adverse reaction to daptomycin. A literature search identified no other reports of hyperkalemia associated with daptomycin use in a patient with normal renal function. CONCLUSION: A 46-year-old women with normal renal function developed hyperkalemia after receiving high-dose daptomycin therapy. The potassium levels normalized when daptomycin was withheld but increased again when the patient was rechallenged with the drug.
Assuntos
Daptomicina/efeitos adversos , Hiperpotassemia/induzido quimicamente , Poliestirenos/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Abscesso/tratamento farmacológico , Administração Oral , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Quelantes/administração & dosagem , Quelantes/uso terapêutico , Daptomicina/administração & dosagem , Daptomicina/uso terapêutico , Feminino , Humanos , Hiperpotassemia/tratamento farmacológico , Pessoa de Meia-Idade , Poliestirenos/uso terapêuticoRESUMO
PURPOSE: To evaluate the in vitro and in vivo effects of three treatment regimens on dentin permeability and reduction of dentin hypersensitivity (DH). METHODS: The desensitization treatments were: Gluma Desensitizer PowerGel (GLU), MS Coat One (MSC), and dentin burnishing with fiber-resin burs (STB). A split-chamber device was used to determine the permeability of dentin slices cut from human molars in vitro. Fluid flow through dentin was recorded with a photochemical method after EDTA cleaning, albumin soaking and desensitization treatment (n = 10). 61 study participants with three severely hypersensitive teeth each were enrolled. Sensitivity was determined with an air stimulus before, immediately after treatment, and after 1, 3 and 6 months, using a verbal rating scale. RESULTS: From the 61 study participants enrolled, 52 completed the trial. Permeability at baseline and after albumin soaking was not significantly different. All treatments produced reduced fluid flow through dentin (P > 0.05). All treatments reduced DH significantly (no or moderate sensitivity). Statistical results revealed significant differences among the treatments (P = 0.03). Mann-Whitney comparisons showed GLU, STB < MSC.
Assuntos
Dessensibilizantes Dentinários/uso terapêutico , Permeabilidade da Dentina/efeitos dos fármacos , Sensibilidade da Dentina/tratamento farmacológico , Adulto , Albuminas/farmacologia , Quelantes/farmacologia , Profilaxia Dentária/instrumentação , Dentina/efeitos dos fármacos , Líquido Dentinal/efeitos dos fármacos , Ácido Edético/farmacologia , Resinas Epóxi/química , Feminino , Seguimentos , Vidro/química , Glutaral/uso terapêutico , Humanos , Masculino , Metacrilatos/uso terapêutico , Pessoa de Meia-Idade , Ácido Oxálico/uso terapêutico , Percepção da Dor/efeitos dos fármacos , Polimetil Metacrilato/uso terapêutico , Poliestirenos/uso terapêutico , Zircônio/químicaRESUMO
We report a newborn girl with life-threatening hyperkalemia and salt wasting crisis due to severe autosomal recessive multiple target organ dysfunction pseudohypoaldosteronism type 1 (MTOD PHA1). She was aggressively managed with intravenous fluids, potassium-lowering agents, high-dose sodium chloride supplementation and peritoneal dialysis. Genetic analysis revealed a homozygous mutation of the α- ENaC (epithelial Na(+) channel) gene. She had a stormy clinical course with refractory hyperkalemia and prolonged hospitalization. Eventually, she succumbed to pneumonia and septicemia at 4 months of age. This is probably the first case of PHA1 confirmed by genetic analysis from India.
Assuntos
Pseudo-Hipoaldosteronismo/terapia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Diálise Peritoneal , Poliestirenos/uso terapêutico , Pseudo-Hipoaldosteronismo/sangueRESUMO
Pseudohypoaldosteronism type 1 is a rare disorder characterized by renal resistance to aldosterone which may present with a salt wasting crisis in infancy. We report a neonate with hyponatremia, severe dehydration and refractory life threatening hyperkalemia who was treated with dietary sodium chloride supplementation, potassium binding resins and fluid replacement therapy which proved to be lifesaving.
Assuntos
Hiperpotassemia/diagnóstico , Hiperpotassemia/terapia , Pseudo-Hipoaldosteronismo/diagnóstico , Pseudo-Hipoaldosteronismo/terapia , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Fludrocortisona/uso terapêutico , Hidratação , Humanos , Recém-Nascido , Masculino , Poliestirenos/uso terapêutico , Bicarbonato de Sódio/uso terapêutico , Cloreto de Sódio/uso terapêuticoRESUMO
Sodium polystyrene sulfonate (SPS) potassium binding resins increase colonic potassium excretion and are approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperkalemia. In 2009, the FDA recommended that sorbitol, a cathartic often given with SPS to prevent obstipation, not be added to SPS powder because of associated colonic necrosis. A premixed oral suspension of SPS in 33% sorbitol was not included in this warning. SPS resins increase stool potassium excretion in normokalemic subjects, but proportionately more potassium is excreted due to cathartics when the two are combined. In hyperkalemic patients, oral SPS mixed in water significantly decreases serum potassium within 24 hours. SPS/sorbitol-associated colonic necrosis is most commonly seen in patients who have received enemas in the setting of recent abdominal surgery, bowel injury, or intestinal dysfunction. It is a rare event, on the order of 0.2 to 0.3%, almost exclusively present in patients at risk. The agent most likely associated with colonic necrosis is 70% sorbitol, and animal data support that etiology. There is very little data to suggest that oral SPS given with 33% sorbitol (in the premixed form) or SPS powder in water orally or as an enema causes colonic necrosis. SPS ion-exchange resins are the only agents, other than dialysis and diuretics, available to increase potassium excretion in hyperkalemia, and when used appropriately, they appear to be clinically effective and reasonably safe.
Assuntos
Catárticos/uso terapêutico , Resinas de Troca de Cátion/uso terapêutico , Hiperpotassemia/tratamento farmacológico , Poliestirenos/uso terapêutico , Potássio/sangue , Sorbitol/uso terapêutico , Animais , Catárticos/efeitos adversos , Resinas de Troca de Cátion/efeitos adversos , Colo/efeitos dos fármacos , Colo/patologia , Combinação de Medicamentos , Sinergismo Farmacológico , Medicina Baseada em Evidências , Fezes/química , Humanos , Hiperpotassemia/sangue , Necrose , Poliestirenos/efeitos adversos , Guias de Prática Clínica como Assunto , Medição de Risco , Sorbitol/efeitos adversos , Resultado do Tratamento , Estados Unidos , United States Food and Drug AdministrationRESUMO
Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.
Assuntos
Colo/patologia , Mucosa Intestinal/patologia , Necrose/induzido quimicamente , Poliestirenos/efeitos adversos , Uremia/fisiopatologia , Adulto , Hemorragia Gastrointestinal/etiologia , Humanos , Hiperpotassemia/tratamento farmacológico , Masculino , Necrose/complicações , Necrose/patologia , Poliestirenos/uso terapêuticoRESUMO
Our objective was to compare the efficacy and safety of rectal cation-exchange resin (Kayexalate) versus salbutamol infusion for the treatment of nonoliguric hyperkalemia (NOHK) in preterm infants. Data of all neonates born with NOHK during the study period of 6 years and 8 months were recorded. Diagnostic criteria of NOHK included serum potassium (SK) concentration > or = 7 mmol/L during the first 72 hours of life with urine output > or = 1 mL/kg/hour. This before-after study was divided according to the date of admission; the first 15 patients were treated with Kayexalate enema 1 g/kg every 4 hours, and the remaining 30 patients were treated with intravenous salbutamol infusion as 4 mug/kg every 4 hours. Treatment discontinued when SK became < 6 mmol/L. SK was measured every 4 hours. Daily urine was collected. Fluid intake and output, serum electrolytes, urea, creatinine, and glucose concentrations were obtained in all infants every 12 hours. All infants were observed with a cardiorespiratory monitor and oxygen saturation and blood pressure measurements. Perinatal characteristics in both groups were comparable. Mean gestational age was 26 and 28 weeks for salbutamol and Kayexalate, respectively. The peak of SK ranged between 7 and 9.3 mmol/L in the Kayexalate group and between 7 and 8.7 mmol/L in the salbutamol group ( P = 0.64). At 12 hours of treatment, SK became normal in only 4 patients (26%) in the Kayexalate group compared with 18 patients (60%) in the salbutamol group ( P = 0.003). The number of doses of Kayexalate administration was significantly higher than the doses of salbutamol ( P = 0.003). No significant side effects were detected in the salbutamol-treated infants. In contrast, there were two cases of severe ventricular tachycardia and one case of intestinal obstruction in the cation-exchange resin group. We concluded that salbutamol infusion is more effective with faster action and safer than cation-exchange resin (Kayexalate) for the treatment of NOHK in preterm infants.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Resinas de Troca de Cátion/uso terapêutico , Hiperpotassemia/tratamento farmacológico , Doenças do Prematuro/tratamento farmacológico , Poliestirenos/uso terapêutico , Feminino , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/urina , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Potássio/sangue , Resultado do TratamentoRESUMO
The development of effective vaginal microbicides is paramount in the fight against the spread of sexually transmitted infections. Preclinical testing of candidate microbicides for the prevention of gonorrhea has been seriously hindered by the lack of an animal model. We assessed the efficacy of 7 promising formulated agents--CarraGuard, Ushercell, [poly]sodium 4-styrene sulfonate (T-PSS), PRO 2000, ACIDFORM, cellulose acetate phthalate (CAP), and BufferGel--by use of a mouse model of Neisseria gonorrhoeae genital tract infection. Mice received test agent, relevant placebo, or no treatment, followed by intravaginal N. gonorrhoeae challenge. N. gonorrhoeae colonization was tested by vaginal culture. CarraGuard, Ushercell, and T-PSS demonstrated significant protection, compared with control agents and no treatment. PRO 2000, ACIDFORM, and CAP showed significant protection, compared with no treatment but not compared with respective control agents. Mice that received BufferGel were provided significant protection, compared with untreated control mice; no placebo was tested. The findings of the present study suggest that topical agents may effectively reduce N. gonorrhoeae infection and that further evaluation is warranted.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Resinas Acrílicas , Animais , Anti-Infecciosos Locais/farmacologia , Modelos Animais de Doenças , Feminino , Géis/uso terapêutico , Gonorreia/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Naftalenossulfonatos/uso terapêutico , Polímeros/uso terapêutico , Poliestirenos/uso terapêutico , Espermicidas/uso terapêutico , Vagina/microbiologiaRESUMO
We report a patient with hepatocellular carcinoma who developed multiple hepatic infarction after transcatheter arterial infusion (TAI) with a suspension of styrene maleic acid neocarzinostatin (SMANCS) and Lipiodol (SMANCS/Lipiodol). The parameters of hepatic functional reserve were apparently decreased after the second TAI with SMANCS/Lipiodol, and the patient died of hepatic failure 103 days after the second TAI. The autopsy liver specimen revealed multiple hepatic infarctions associated with peripheral arterial stenosis or occlusion, and portal thrombosis. It is speculated that both the arterial occlusion and the portal thrombosis caused the hepatic infarction, based on a long-term insufficiency of blood supply to the hepatocytes arising from toxic arteritis caused by SMANCS/Lipiodol.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Cateterismo , Infarto/induzido quimicamente , Infusões Intra-Arteriais/instrumentação , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Fígado/irrigação sanguínea , Anidridos Maleicos/administração & dosagem , Anidridos Maleicos/efeitos adversos , Poliestirenos/administração & dosagem , Poliestirenos/efeitos adversos , Zinostatina/administração & dosagem , Zinostatina/efeitos adversos , Meios de Contraste/uso terapêutico , Humanos , Infarto/etiologia , Óleo Iodado/uso terapêutico , Masculino , Anidridos Maleicos/uso terapêutico , Pessoa de Meia-Idade , Poliestirenos/uso terapêutico , Zinostatina/análogos & derivados , Zinostatina/uso terapêuticoRESUMO
We described a 10 day old boy who presented with hyponatremia, hyperkalemia, and metabolic acidosis. Therapeutic treatment with exogenous glucocorticoid and mineralocorticoid for 8 months failed to correct the electrolyte abnormalities. The elevated serum cortisol up to 44.34 micrograms/dl along with the absence of skin hyperpigmentation excluded defects in the glucocorticoid pathway. Pseudohypoaldosteronism was diagnosed on the basis of hyponatremia, severe urinary salt loss despite the markedly elevated serum aldosterone up to 6,500 pg/ml (normal range 50-800 pg/ml). The patient responded very well to oral salt supplementation and cation exchange resin therapy shown by normal physical growth and normal levels of serum electrolytes.
Assuntos
Pseudo-Hipoaldosteronismo/diagnóstico , Pseudo-Hipoaldosteronismo/tratamento farmacológico , Aldosterona/sangue , Diagnóstico Diferencial , Eletrólitos/sangue , Humanos , Hidrocortisona/sangue , Recém-Nascido , Masculino , Poliestirenos/uso terapêutico , Pseudo-Hipoaldosteronismo/classificação , Pseudo-Hipoaldosteronismo/genética , Pseudo-Hipoaldosteronismo/metabolismo , Cloreto de Sódio/uso terapêuticoRESUMO
PURPOSE: Staphylococcus aureus causes severe corneal infections that often result in corneal scarring and blindness. Presently, therapy often involves the use of a fluoroquinolone antibiotic. This study, employing an experimental rabbit model of Staphylococcus keratitis, compared the effectiveness of two commonly prescribed formulations of fluoroquinolones to an experimental formulation, ciprofloxacin with polystyrene sulfonate (ciprofloxacin-PSS). The ciprofloxacin-PSS formulation uses an ion exchange resin to aid in the delivery of drug to the cornea. METHODS: Early (4-9 h postinfection, PI) and late (10-15 h PI) therapies were studied, employing 5 groups: ciprofloxacin-PSS, ciprofloxacin, ofloxacin, PSS vehicle. and untreated. Dosing regimens were: every 30 min, 60 min, or a single drop applied at 9 h PI. Eyes were observed by slit lamp examination (SLE) and bacterial colony forming units (CFU) per cornea were determined. RESULTS: Early phase therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min were equally effective (P > or = 0.2880), decreasing CFU per cornea by >5 log. Ciprofloxacin was significantly more active than ciprofloxacin-PSS or ofloxacin (P < or = 0.0410) when applied as a single drop. Late therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min resulted in >3 log decrease in CFU per cornea relative to controls (P < or = 0.0001). CONCLUSIONS: Topical treatment of experimental Staphylococcus keratitis with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin was effective. The effectiveness of ciprofloxacin-PSS suggests that improved drug delivery systems employing an ion exchange resin could be useful in an ocular fluoroquinolone formulation.
Assuntos
Anti-Infecciosos/uso terapêutico , Ciprofloxacina/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Ofloxacino/uso terapêutico , Poliestirenos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Ciprofloxacina/análogos & derivados , Contagem de Colônia Microbiana , Córnea/microbiologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Infecções Oculares Bacterianas/microbiologia , Ceratite/microbiologia , Soluções Oftálmicas , Coelhos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
To assess the efficacy of the zinostatin derivative, the anti-tumor agent, styrene-maleic acid neocarzinostatin, in treating multiple small liver cancers, 29 patients with multiple hepatocellular carcinoma of 3 cm or less in diameter were treated with intraarterial injections of this high molecular weight agent, mixed with Lipiodol. Computed tomography 3 months after the first therapy showed complete deposition of Lipiodol in the entire area of the original tumor in 8 patients (27.6%), 50%-99% deposition in 4 (13.8%), 10%-49% in 10 (34.5%), and less than 10% in 7 (24.1%). After repeated injections, Lipiodol deposition in the entire area of the original tumor was found in 11 patients (37.9%). The degree of Lipiodol deposition depended on the angiographic vascularity of the tumor and on the images of the computed tomogram during arterial portography. Although complete deposition of Lipiodol was found in all tumors in 10 (58.8%) of the 17 patients with well demarcated round hypervascularity, only 1 (8.3%) of 12 patients with ill demarcated tumors showed complete deposition of Lipiodol in the tumors. Taking into account that hypervascularity on angiograms was closely correlated with the degree of Lipiodol accumulation on computed tomograms taken later, it appears that well demarcated round-shaped liver cancer is the best candidate for styrene-maleic acid neocarzinostatin therapy.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Anidridos Maleicos/uso terapêutico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Poliestirenos/uso terapêutico , Zinostatina/análogos & derivados , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Meios de Contraste/farmacologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Injeções Intra-Arteriais , Óleo Iodado/farmacologia , Neoplasias Hepáticas/mortalidade , Masculino , Anidridos Maleicos/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Poliestirenos/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Zinostatina/administração & dosagem , Zinostatina/uso terapêutico , alfa-Fetoproteínas/análiseAssuntos
Fosfatos de Cálcio/uso terapêutico , Resinas Compostas/uso terapêutico , Infiltração Dentária/prevenção & controle , Adesivos Dentinários/uso terapêutico , Metacrilatos/uso terapêutico , Poliestirenos/uso terapêutico , Timol/análogos & derivados , Coroa do Dente , Forramento da Cavidade Dentária , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Guta-Percha/uso terapêutico , Humanos , Técnicas In Vitro , Materiais Restauradores do Canal Radicular/uso terapêutico , Obturação do Canal Radicular , Timol/uso terapêutico , Cimento de Óxido de Zinco e Eugenol/uso terapêuticoAssuntos
Antineoplásicos/farmacocinética , Anidridos Maleicos/farmacocinética , Neoplasias/irrigação sanguínea , Poliestirenos/farmacocinética , Zinostatina/análogos & derivados , Antineoplásicos/uso terapêutico , Permeabilidade Capilar , Carcinoma Hepatocelular/tratamento farmacológico , Portadores de Fármacos , Humanos , Óleo Iodado , Neoplasias Hepáticas/tratamento farmacológico , Anidridos Maleicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Poliestirenos/uso terapêutico , Zinostatina/farmacocinética , Zinostatina/uso terapêuticoRESUMO
The authors present the case of a patient who developed near total colonic necrosis shortly after renal transplantation. The onset of symptoms was temporally related to the administration of sodium polystyrene (Kayexalate; Sanofi Winthrop Pharmaceuticals, New York, NY)-sorbitol enemas for treatment of hyperkalemia. Three similar cases have been reported in the literature. The presence of uremia and the use of sorbitol appear to be common denominators in the pathophysiology of this complication. It is suggested that Kayexalate-sorbitol enemas be avoided in renal transplant patients.
Assuntos
Colo/patologia , Enema/efeitos adversos , Transplante de Rim , Poliestirenos/efeitos adversos , Humanos , Hiperpotassemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Poliestirenos/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológicoRESUMO
Myocardial calcification has been rarely described in premature infants after myocardial infarction and myocarditis with coxsackievirus B1. In adults and older children, metastatic myocardial calcification has been reported in chronic renal failure. We report a case of myocardial calcification in a 680-gm preterm infant after a prolonged course of renal failure complicated by secondary hyperparathyroidism. Subclinical myocardial injury was evidenced by a high serum creatine phosphokinase MB band concentration, which probably provided a susceptible substrate for the deposition of calcium crystals, because the multiplication product of serum calcium and inorganic phosphorus levels transiently exceeded 75 mg x mg/100 ml, indicating serum saturation during the course of secondary hyperparathyroidism. We report this case as an unusual complication of renal immaturity in extremely low birth weight infants and an indication of a relatively intact parathyroid glandular function in them. Hypoxia, myocardial dysfunction, and renal failure are common complications in such infants, and in the presence of renal failure, the serum levels of calcium and inorganic phosphorus should be maintained below the pathologic level to avoid ectopic calcification of the tissues, including the myocardium.